Osteoporosis and its sequelae pose a substantial health burden for postmenopausal women. One white woman in six will suffer a hip fracture during her lifetime, and mortality after hip fracture ranges from 12-20% in the first year. Nutritional supplements to optimize dietary intake can improve bone health. For example, dietary calcium and vitamin D intake is often sub-optimal; supplements can reduce bone loss and fracture risk. Less well known is that the typical diet of industrialized nations is also deficient in potassium and base precursors (fruit and vegetables) while being rich in acid precursors (protein). The lack of dietary base precursors results in a mild metabolic acidosis that becomes progressively worse due to age related declines in renal function. Even the mild degrees of metabolic acidosis that occur with aging increase urinary calcium excretion, bone resorption, and urinary nitrogen excretion as base is mobilized from bone and muscle to buffer the dietary acid. These changes can be reversed by dietary supplementation with base as an alkaline potassium salt (e.g. potassium citrate). Combination therapy with a thiazide diuretic and an alkaline salt of potassium lowers urinary calcium excretion even further. To test the hypothesis that supplementation with oral potassium citrate, thiazide diuretic, or combination therapy with both agents will reduce bone and muscle mass loss over three years in postmenopausal women, they plan a randomized, double-blind, placebo-controlled trial. This will be a large multi-center study with an estimated sample size of 3220 participants, requiring extensive development and planning. Therefore, they are submitting this proposal for a planning grant to develop the specific elements essential for a successful full-scale clinical trial including strategies for recruitment of participants, experimental design and protocols, data management, analytical techniques, administrative procedures, and collaborative arrangements.